Molecular docking and dynamics simulations revealed the potential inhibitory activity of honey-iQfood ingredients against GSK-3β and CDK5 protein targets for brain health

• Published in: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
• Main Authors: Zakaria, Nor Hafizah; Mohamed Tap, Fatahiya; Aljohani, Ghadah Faraj; Abdul Majid, Fadzilah Adibah
• Format: Article; Early Access
• Language: English
• Published: TAYLOR & FRANCIS INC 2023
• Subjects: Biochemistry & Molecular Biology; Biophysics
• Online Access: https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001137873000001
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2023.2298726

Honey-iQfood is an herbal supplement made of a mixture of polyherbal extracts and wild honey. The mixture is traditionally claimed to improve various conditions related to brain cells and functions including dementia and Alzheimer's disease. Glycogen synthase kinase-3 beta (GSK-3 beta) and cyclin-dependent kinase 5 (CDK5) have been identified as being involved in the pathological hyperphosphorylation of tau proteins, which leads to the formation of neurofibrillary tangles and causes Alzheimer's disease. Therefore, this study was conducted to confirm the traditional claims by detection of active compounds, namely curcumin, gallic acid, catechin, rosmarinic acid, and andrographolide in the raw materials of Honey-iQfood through HPLC analysis, molecular docking, and dynamic simulations. Two potential compounds, andrographolide, and rosmarinic acid, produced the best binding affinities following the molecular docking of the active compounds against the GSK-3 beta and CDK5 targets. Andrographolide binds with GSK-3 beta at -8.2 kcal/mol, whereas rosmarinic acid binds to CDK5 targets at -8.6 kcal/mol. Molecular dynamics was further carried out to confirm the docking results and clarify their dynamic properties such as RMSD, RMSF, rGyr, SASA, PSA, and binding free energy. CDK5-andrographolide complexes had the best MM-GBSA score (-83.63 kcal/mol) compared to other complexes, indicating the better interaction profile and stability of the complex. These findings warrant further research into andrographolide and rosmarinic acid as efficient inhibitors of tau protein hyperphosphorylation to verify their therapeutic potential in brain-related illnesses.